Rao Lab

"The immune system is an ideal model for studying all sorts of biochemical processes - development, the regulation of gene expression, alternative splicing and cellular stress responses, to mention only a few." — Anjana Rao, Ph.D. // Professor, Division of Signaling and Gene Expression Pfizer Endowed Chair in Cancer Immunology and Oncology

Overview

Our research has been focused on understanding how signalling pathways control gene expression, using T cells and other cells of the immune system as models. There are several aspects to our research. We are particularly interested in a pathway of gene expression that is regulated by calcium influx into many different types of cells: it involves a process known as store-operated calcium entry, which activates a phosphatase, calcineurin, which dephosphorylates and sends a transcription factor, NFAT, to the nucleus. NFAT turns on a large number of genes, in a manner appropriate to the cell type and mode of stimulation; in T cells, it controls both the positive transcriptional programmes of T cell activation and negative programmes known as anergy or exhaustion that attenuate T cell activation. We are using RNA interference and CRISPR/Cas9 screens, mice with targeted gene disruption, high-throughput sequencing and other technologies to analyze how genes are regulated and how loss of function of certain proteins leads to diseases such as autoimmunity, immune deficiencies, developmental defects and cancer. A current important focus involves the TET family of 5-methylcytosine oxidases, which control cell lineage specification in many different systems. Profound TET loss-of-function is associated with aggressive cancers, both in human and in mouse model systems, and we are examining the mechanisms involved.

Principal Investigator

Anjana Rao, Ph.D.

Professor, Division of Signaling and Gene Expression

A member of the National Academy of Sciences, Dr. Rao received her undergraduate and master’s degrees from Osmania University in India and her Ph.D. from Harvard University. After many years as a faculty member at the Harvard Medical School and the Immune Disease Institute in Boston, she joined the La Jolla Institute in 2010. She has worked on signaling and gene transcription for many years, is a member of numerous advisory panels, and has received several major awards.

Lab Members

Michael Allevato

Graduate Student

Sanjana Balagere

Intern

Bokan Bao

Graduate Student

Joyce Chen

Graduate Student

Biosketch:
Joyce Chen received her BS in Biochemistry from the University of California, Los Angeles (UCLA). She then worked as a research associate at the California Institute of Technology (Caltech) in the laboratory of Dr. David Baltimore, where she helped develop an adeno-associated virus (AAV)-based HIV prophylaxis. Currently, Joyce is a MD/PhD student at the University of California, San Diego (UCSD), and she is doing her thesis work in the laboratory of Dr. Anjana Rao at the La Jolla Institute for Allergy and Immunology.

Research Focus:
Joyce is working to elucidate the roles of these transcription factors in CD8 T cell exhaustion.

Joanna Coker

Graduate Student

Benjamin Delatte

Postdoctoral Fellow

Biosketch:
Benjamin Delatte is an HHMI fellow from the Jane Coffin Childs foundation. He has performed his Ph.D training in Prof. François Fuks’ laboratory in Belgium at the time that TET function was discovered by the team of Dr. Anjana Rao. Applying proteome and genome-wide approaches, he found that the most potent partner of TETs is the glycosyltransferase OGT (Deplus*, Delatte* et al., Embo, 2013), and recently discovered that Tet is responsible for RNA hydroxymethylation in drosophila (Delatte et al., Science, 2016).

Research Focus:
Ben is now investigating the roles of TETs and hydroxymethylcytosine in genomic instability and cancer. He is also developing novel methodologies to map epigenetic modifications, and to identify diverse hallmarks of cancer such as DNA breaks or aberrant DNA:RNA structures

Dina Faddah

Visiting Scientist

Marlet Morales Franco

Intern

Romain Georges

Postdoctoral Fellow

Ryoichi Hayakawa

Visiting Scientist

Laura Hempleman

Research Technician I

Jad Kanbar

Graduate Student

Xiang Li

Instructor

Biosketch:
Xiang Li received his undergraduate degree from Nanjing University in 2005. From there, he proceeded to receive his Ph.D. in Stem Cell Research and Developmental Biology at the Institute of Health Sciences at the Chinese Academy of Sciences in Shanghai, China in 2011. Xiang Li’s is currently an instructor in Dr. Anjana Rao’s lab at the La Jolla Institute for Allergy and Immunology.

Research Focus:
Xiang Li’s research is focused on the role of Tet family in cardiac and neural cell fate determination in mouse embryonic stem cells.

Matthias Lienhard

Visiting Scientist

Chan-Wang (Jerry) Lio

Instructor

Biosketch:
Jerry Lio received his undergraduate and master’s degree in Microbiology and Immunology at National Yang-Ming University in Taiwan. Mentored by Dr. Chyi-Song Hsieh, he later obtained his Ph.D. from Washington University in St. Louis with a focus on the thymic development of Foxp3+ regulatory T cells. Currently he is an instructor at Dr. Anjana Rao’s lab at La Jolla Institute for Allergy and Immunology.

Research Focus:
Jerry’s research focuses on understanding the roles of TET proteins and DNA cytosine hydroxymethylation in the function and transformation of B cells.

Isaac Lopez-Moyado

Graduate Student

Biosketch:
Isaac F. López-Moyado received his B.S. in Genomic Sciences from the National Autonomous University of Mexico (UNAM), and completed his undergraduate degree while doing research in the laboratory of Walter Fontana at Harvard Medical School (HMS) where he worked on aging in C. elegans and lifespan distributions. After graduating from UNAM, Isaac started his Ph.D. in the Bioinformatics and Systems Biology program at the University of California, San Diego (UCSD), where he is mentored by Dr. Anjana Rao.

Research Focus:
Isaac’s research focuses on the role of TET proteins and oxidized methylcytosines in maintaining genome integrity, and their relationship to oncogenesis.

Atsushi Onodera

Postdoctoral Fellow

Biosketch:
I graduated from the University of Tokyo in 2002 with a Bachelor of Science degree in Chemistry and Biotechnology. I then moved to Chiba University, School of Medicine, and finished M.D.-Ph.D. course in 2010. Directly after that, I began working as an Assistant Professor at the Chiba University, Graduate School of Medicine. In 2016, I got an Associate Professor positon in the Global Prominent Research Institute at Chiba University, which promotes international collaboration between the University of California, San Diego (UCSD) and Chiba University. That is one of the reasons I began working as a Postdoctoral Fellow at the La Jolla Institute for Allergy and Immunology (LJI) in July of 2017.

Research Focus:
For the past several years my research has been focused on the study of the epigenetic regulation of T-cells in the context of their functions in the immunological memory. Particularly, Polycomb and Trithorax proteins, which methylate histone H3-K27 and K4, respectively, have been of interest to me. In the LJI, I will study the roles of 5-hydroxymethylcytosine (5hmC) in T-cell-mediated immune responses, mainly focusing on its role in DNA demethylation.

Career Goals:
Goals in my career in scientific research are as follows:
1. Clarify the molecular basis of the immunological memory.
2. Induce general principles or laws from big data (e.g. next generation sequencing).
3. Apply the knowledge acquired from the basic research to the treatment of intractable diseases.

Homa Rahnamoun

Graduate Student

James Scott-Browne

Postdoctoral Fellow

Vipul Shukla

Postdoctoral Fellow

Biosketch:
Vipul Shukla received his undergraduate degree in Zoology from the University of Delhi in New Delhi, India in 2007, and then proceeded to receive his master’s degree in Toxicology from Jamia Hamdard University in New Delhi, India in 2009. He later obtained his Ph.D. from the University of Nebraska Medical Center in Omaha, Nebraska in 2016 with a focus on Genetics, Cell Biology and Anatomy. Currently, he is a postdoc in Dr. Anjana Rao’s lab at La Jolla Institute for Allergy and Immunology.

Research focus:
Vipul’s research focus is on investigating the role of TET proteins as regulators of genomic stability.

Angeliki Tsangaratou

Instructor

Biosketch:
I received my bachelor in Biology from the National and Kapodistrian University in Athens Greece and my PhD in Immunology from the Aristotle university of Thessaloniki in Greece. I joined the Rao lab in the La Jolla Institute in November and 2010 and was promoted to Instructor in 2013.

Research Interests:
I am working on the regulation of gene expression in T cell development. My aim is to dissect how aberrations of the differentiation process can result in autoimmunity or malignant transformation and cancer emergence.

Victor Wong

Postdoc

Robyn Wygal

Graduate Student

Xiaojing Yue

Instructor

Biosketch:
Xiaojing received her undergraduate degree from Jilin University in Changchun, China in 2004, and then proceeded to obtain her master’s from the Institute of Microbiology at the Chinese Academy of Sciences in Bejing, China in 2007. Then in 2011, she received her Ph.D. in Immunology under the mentorship of Dr. Tilman Borggrefe from the Max-Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. Currently, she is an instructor in Dr. Anjana Rao’s lab at La Jolla Institute for Allergy and Immunology.

Research Focus:
Xiaojing’s research focuses on the role of TET proteins in regulatory T cells and mechanistic regulation of regulatory T cell stability.

Hiroshi Yuita

Shen Zeyang

Wade Zhang

Graduate Student

Biosketch:
I am a bioengineering Ph.D. student at the University of California, San Diego. I work in Anjana Rao’s lab at the La Jolla Institute for Allergy and Immunology.

Research focus:
Engineer the immune system to better fight disease. I’m testing ways to prevent CD8 cell exhaustion. CD8 cells can become exhausted if they encounter antigen for prolonged times like in a chronic infection or large tumor. Exhausted CD8 cells cannot effectively kill their targets and preventing CD8 exhaustion will help them survive longer to kill more of their targets.

Career goal:
Use the immune system to develop cellular therapies that fight diseases like cancer, infection, and autoimmunity.